Just a phage we're going through

Antibiotic resistance? Why not try phage therapy

By Katherine Addleman

Bacterial antibiotic resistance is growing by leaps and bounds, threatening to throw us back to the pre-penicillin dark ages. There are now hospital bugs that just laugh at our biggest guns like methicillin and vancomycin. Tons of antibiotics are thrown into livestock feed and fish farms virtually unchecked, guaranteeing that we'll be confronted with new superbugs. Overprescribing, though on the decline, is still rampant.

Luckily, help might be right under our noses according to a recent article in the Journal of the American Medical Association -- in the form of an old, familiar friend, the bacteriophage, or phage.

A phage is a virus that only attacks bacterial cells, making it, by definition, harmless to plants or animals. These natural predators of bacteria target a specific microbe, leaving non-target bacteria -- the normal friendly flora that cover our skin and thrive in our gut, unharmed. Evidence of phage activity was first published in 1896. Twenty years later, Felix d'Herelle from the Pasteur Institute in France figured out that some mysterious entity existed that was lethal to bacteria. He founded the Eliava Institute in Tbilisi, Georgia for the purpose of phage research. Phages were used sporadically in the West, sometimes with spectacular results, but the arrival of antibiotics in the 1940s sounded the death knell for phage therapy here.

In Stalinist Russia and the postwar Soviet Union, however, phage therapy flourished. It was the standard treatment for infection for the Soviet Army, and it's still considered the gold standard for conditions like diabetic ulcers, in which poor circulation reduces the usefulness of modern antibiotics.

With the spectre of antibiotic resistance looming, scientists in the West are turning to the treasure trove of phage information gleaned through decades of experience at the Eliava Institute and elsewhere.

Dozens of Western biotechnology companies are scrambling to learn from the Russian experience and develop products to combat the increasingly antibiotic-resistant bacterial community. Among these is a Montreal company, PhageTech, which is studying phage "killer" proteins that help the virus commandeer the bacterial host for more efficient phage replication. Another Montreal firm, Biophage Pharma, is developing phages against the scourge of chicken-linked salmonella and pathogenic strains of E coli.

Complicated government regulations have made clinical trials in humans virtually impossible for now. So a lot of companies have turned to studying the use of phage in agricultural settings and food processing. An American company called Intralytix has shown that phage can keep peeled and cut fruits and vegetables free of those nasty food poisoning pests, Listeria and salmonella, at no risk to human consumers. This makes it ideal for use in salad bars or on items like bean and alfalfa sprouts. Other American firms are investigating phage control of common food-poisoning bugs in chicken, and of the dreaded E coli 0157:H7 in beef. That's the bacterial strain that caused millions of tons of beef to be recalled in the US last year and is responsible for many deaths annually. Biophage Pharma is also working on phage control of bacterial contaminants in food processing. Oysters and beef cattle are now being tested to see if they can be grown free of pathogens through treatments with phage.

Researchers at Rockefeller University in New York are trying a novel approach using enzymes from phages rather than the whole virus. The enzymes are still specific -- that is, they only attack the target pathogen and are harmless to neighbouring microbes. The researchers isolate the useful enzymes, sequence the genes that encode them and manufacture them in bulk via recombinant biotechnology. The means of administration? A simple nasal spray. The spray approach could also be ideal for contaminated wounds or for spraying on processed or exposed fruits and vegetables. Enzyme preps could also be administered intravenously. And they could be used prophylactically, for example, to prevent catheter contamination.